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Mechanism of action of Nimodipine

Apr 29，2022

Nimodipine is a dihydropyridine-type CCB used as anti-hypertensive agent. Due to its highly lipophilic properties itreadily crosses the blood-brain barrier (BBB), affects auto-regulation of CBF and produces vasodilatation of small cere-bral blood vessels.

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Mechanism of action

Nimodipine reduces the severity of neurological outcome after subarachnoidhaemorrhage (SAH) secondary to ruptured aneurysms,probably by decreasing cerebral vasospasm,although thiseffect has not been demonstrated by angiography or tran-scranial Doppler.In addition to itsvascular effects, nimodipine appears to have nootropic prop-erties.There is a high density of nimodipine-binding sites in hippocampus, caudate nucleus and cerebral cortex.

Nimodipine binds to slow L-type calciumreceptors, preventing influx of calcium into vascular smoothmuscle cells and into ischaemic neurones; experimentally,it protects against age-associatedmicrovascular abnormalities in the rat brain.Although a neuroprotective effecthas been postulated in stroke patients, nimodipine showedonly a trend for better outcome when used within the first 12hours of stroke onset.

Trial

A reanalysis of the Scandinavian Trial of Nimodipinein MID showed a beneficial effect intests of attention and psychomotor performance in the sub-group of patients with subcortical small vessel VaD, but notin patients with PSD of the MID type. A pilot open-labeltrial of nimodipine in patients with small vessel VaD waspositive.In this study, subcortical VaDwas defined according to ICD-10 criteria, and inclusion criteria required thepatients to have mild-to-moderate dementia (MMSE12-24,GDS 3-5), as well as CT evidence of extensive leukoara-iosis and at least one lacunar infarct.The primary measureof efficacy was the Sandoz Clinical Assessment - Geriatric(SCAG) scale.

Using similar criteria and outcome measures，a largemulticentre,double-blind,placebo-controlled RCT ofnimodipine in subcortical VaD was conducted in Italy andSpain.Of 242 patients randomized tonimodipine 90 mg/day or placebo, 230 patients (nimodipineN= 12l, placebo N= i09) were included in the intention-to-treat analysis.At 52 weeks, there was no difference in theprimary outcome measure (SCAG scale) between the twogroups.However, patients on nimodipine performed betterthan placebo in lexical production (p <0.01),MMSE (p<0.01) and GDS (p <0.05).

More dropouts and AEs occurredamong the placebo group (cardiovascular and cerebrovas-cular events, and behavioural disturbances requiring inter-vention). The authors concluded that nimodipine offersbenefit in subcortical VaD and might protect against car-diovascular and CVD comorbidities in this high-risk group. A Cochrane review on nimodipine found no convincing evidence for its efficacy inAD, VaD or mixed forms of dementia.

Side-effects

The FDA has classified the side effects into groups based on dosages levels at q4h. For the high dosage group (90 mg) less than 1% of the group experienced adverse conditions including itching, gastrointestinal hemorrhage, thrombocytopenia, neurological deterioration, vomiting, diaphoresis, congestive heart failure, hyponatremia, decreasing platelet count, disseminated intravascular coagulation, deep vein thrombosis.[

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